CACR13 is now out featuring updates on the ISO 14644 series of standards and much else. For more information or to subscribe please visit CACR or contact John Neiger via LinkedIn and request the Contents and Abstracts.

CACR is a quarterly technical journal supported by subscribers and advertisers and it is my intention to keep it technical rather than commercial. Most articles are commissioned by me, but if you would like to write an article on any aspect of cleanroom or containment technology I would be very pleased to hear from you.

Whilst writing can I also tell you about a new book that is coming out very shortly. It is called Cleanroom Management in Pharmaceuticals and Healthcare, edited by Tim Sandle and Madhu Raju Saghee. I was involved in chapter 9: Fundamentals of pharmaceutical isolators. For more information or to order please contact the publisher. There is a very interesting pre-publication offer!

Best wishes

John

John Neiger, Editor Clean Air and Containment Review – The journal to enhance your knowledge of cleanroom, clean air and containment technology

An
international study has revealed that a new strain of the MRSA has made a leap
from food animals to humans. Scientists from 20 institutions have conducted a
research project focusing on the MRSA CC398 strain, known as pig MRSA or
livestock-associated MRSA due to its prevalence among farm workers.

The
study was led by Translational Genomics Research Institute (TGen).

Whole
genome sequencing has shown that it was most likely an antibiotic-susceptible
strain in humans in the past before transferring to food animals, where it
became resistant to tetracycline and methicillin due to routine antibiotic use
among animals to prevent staph infections.

This
excessive application of antibiotics has caused the disease to rapidly evolve
and spread back to humans.

The
research was published in PLoS on-line and was titled “Persistence of Livestock
Associated MRSA CC398 in Humans Is Dependent on Intensity of Animal Contact”.

The
introduction to the paper reads:

“The
presence of Livestock Associated MRSA (LA-MRSA) in humans is associated with
intensity of animal contact. It is unknown whether the presence of LA-MRSA is a
result of carriage or retention of MRSA-contaminated dust. We conducted a
longitudinal study among 155 veal farmers in which repeated nasal and throat
swabs were taken for MRSA detection. Periods with and without animal exposure
were covered.”

This
day at the end of February marks the sixth international Rare Disease Day.

On
and around this day hundreds of patient organisations
from more than 60 countries and regions worldwide are planning
awareness-raising activities converging around the slogan “Rare Disorders
Without Borders”.

Activities
will take place across Europe, all the way to Russia, continuing to China and
Japan, in the US and Canada, and as far as Australia and New Zealand.

Wednesday, 27 February 2013

The
IEST has revised its standard for Product Cleanliness Levels – Applications,
Requirements, and Determination.

This
standard provides methods for specifying and determining product cleanliness
levels for contamination-critical products. The emphasis is on contaminants
that can impact product performance.

The
requirements set forth in this standard are not required for all products but
are intended for use in procurement and design contracts for those items where
contamination control limits for parts, components, or fluids are necessary to
ensure reliability and performance.

This
standard provides mutually agreed-upon limits for defining significant surface
cleanliness and liquid cleanliness with respect to particles and molecular
residue. The standard has been modified to include alternative cleanliness
level designations that are better suited to accommodate user-specific applications.
These modifications are included in informative annexes at the end of the
document.For further details see IEST.

A
book of interest has been published on biofilms, the book is titled “Microbial
Biofilms: Current Research and Applications”.

The
book synopsis reads:

“Biofilms
are the default mode-of-life for many bacterial species. The three-dimensional
structure of the biofilm provides the associated microbial communities with
additional protection from predation, toxic substances and physical
perturbation. The variety of microniches provided by the biofilm also promotes
a huge diversity of microbial life and metabolic potential. These complex and
highly structured communities help to maintain the health of soils and waters.
Current applications of biofilms include the degradation of toxic substances in
soil and water, the commercial production of chemicals, and the generation of
electricity. However, biofilm-based infections cause harm to millions of humans
annually. In addition, biofilms can affect the quality and yield of crops and
cause biofouling and microbially-induced corrosion.

In
this book, leading scientists provide an up-to-date review of the latest
scientific research on these fascinating microbial communities and predict
future trends and growth areas in biofilm-related research.

Under
the expert guidance of the editors Gavin Lear and Gillian Lewis, authors from
around the world have contributed critical reviews on the most topical aspects
of current biofilm research. Subjects covered include quorum sensing and social
interactions in microbial biofilms, biofilms in disease, plant-associated
biofilms, biofilms in the soil, applications in bioremediation, biofilms in
wastewater treatment, corrosion and fouling, aquatic biofilms, microbial fuel
cells, and catalytic biofilms. The book is essential for everyone interested in
biofilms and their applications. It is also highly recommended for
environmental microbiologists, soil scientists, medical microbiologists,
bioremediation experts and microbiologists working in biocorrosion, biofouling,
biodegradation, water microbiology, quorum sensing and many other areas.”

The
details are:

Publisher:
Caister Academic Press

Editor:
Gavin Lear and Gillian D. Lewis Lincoln University, Christchurch, New Zealand
and University of Auckland, New Zealand (respectively)

Tuesday, 26 February 2013

Diphtheria is a serious disease caused by a toxin made by a type of bacteria known as Corynebacterium diphtheria. The toxin alters protein function in people with the condition. Currently there are several subspecies of the Gram positive bacteria recognized by scientists.

Respiratory diphtheria manifests as a sore throat with low-grade fever and an adherent pseudomembrane of the tonsils, pharynx, or nose. Another form of the disease is known as cutaneous diphtheria. People with this condition have infected skin lesions which typically lack a characteristic appearance.

On this subject, the IAQ Video Network and Cochrane & Associates have announced the release of another online video to help educate the public about issues that may impact their health. Their latest educational video discusses Corynebacterium diphtheria and diphtheria.

The European Commission has announced it will launch an
observatory to map progress and impact of the development of the EU's
bioeconomy.

The observatory, which is part of the EC's bioeconomy action plan, will
gather data to follow the evolution of markets, to map EU, national and
regional bioeconomy policies, research and innovation capacities, and
the scale of related public and private investments. The Commission's
in-house science service JRC will run the new resource.

The observatory will start its 3-year term in March 2013 with the aim of
making the data it will collect publicly available through a dedicated
web portal in 2014. In this way, the observatory will support the
regional and national bioeconomy strategies
now being developed by EU Member States. The observatory will track a
number of performance measures, including economic and employment
indicators, innovation indicators, and measures of productivity, social
wellbeing and environmental quality.

Monday, 25 February 2013

The EU-project PharmaSea will bring researchers to some
of the deepest, coldest and hottest places on the planet in the hunt for
novel antibiotics.

Marine organisms that live more than 6,000 meters below the sea level
are considered to be an interesting source of novel bioactive compounds
as they survive under extreme conditions.

Scientists from the UK, Belgium, Norway, Spain, Ireland, Germany,
Italy, Switzerland and Denmark will work together to collect and screen
samples of mud and sediment from huge, previously untapped, oceanic
trenches. The large-scale, four-year project is backed by more than €9.5
million of EU funding and brings together 24 partners from 14 countries
from industry, academia and non-profit organisations.
The PharmaSea project
focuses on biodiscovery research and the development and
commercialisation of new bioactive compounds from marine organisms,
including deep-sea sponges and bacteria, to evaluate their potential as
novel drug leads or ingredients for nutrition or cosmetic applications.

Saturday, 23 February 2013

Microorganisms found in pharmaceutical and healthcare environments require identification in order to determine the species. This is important so that the origin of contamination can be assessed and the origin of contamination determined. This is commonly performed by using a standing technique called the Gram stain, which is based is a type of "phenotypic identification method" and it undertaken so that the microbiologist can understand the general profile for microorganisms.

The first step of most identification schemes is to describe the colony and cellular morphology of the microorganism. Colony morphology is normally described by directly observing growth on agar, where the colony will appear as a particular shape (such as raised, crenated, spherical and so on) and the colony will have a particular pigment. Some microbiologists will attempt to identify the microorganism based on such visual identification. This is not normally encouraged as considerable experience is required to do this and the variety of microflora cannot be characterised with any degree of accuracy. Furthermore, the characteristics of a microorganism are often dependent upon the type of culture medium used. Nevertheless, a description of the morphology can assist with further stages of identification.

Cellular staining provides important information relating to the composition of the microbial cell wall, as well as the shape of the organism. Of these, the most frequently used method is the Gram stain.

The Gram stain method employed includes the four-step technique: Crystal violet (primary stain); iodine (mordant); alcohol (decolorizer); and safranin (counter stain). Done correctly, Gram-positive organisms retain the crystal violet stain and appear blue; Gram negative organisms lose the crystal violet stain and contain only the counter-stain safranin and thus appear red. Common pitfalls in this method are that heat fixation may cause Gram-positive cells to stain Gram-negative and older cultures may give Gram-variable reaction; using too much decolorizer could result in a false Gram-negative result and not using enough decolorizer may yield a false Gram-positive result.

The Gram reaction is based on the differences in the cell wall composition for the two cellular 'groups'. The bacteria that retained the stain (the Gram-positive bacteria) have a higher peptidoglycan and lower lipid content than those that do not retain the stain (the Gram-negative bacteria). The effect of the solvent is to dissolve the lipid layer in the cell wall of the Gram-negative bacteria, thereby causing the crystal violet to leach out; whereas for Gram-positive bacteria the solvent dehydrates the thicker cell walls, blocking any diffusion of the violet-iodine complex, which closes the pores of the cell and retains the stain. There are now several automated Gram stain devices available on the market that can reduce the labour requirement required when performing several multiple Gram stains and, possibly, improve accuracy.

In addition to the difference based on cell wall, microscopic examination of the stains allows the cellular shape to be determined. Bacteria commonly fall into the categories of coccus (spherical), rod, vibrio (curved), spirilla (spiral) and plemomorphic (variable).

Friday, 22 February 2013

The issue of beta-glucans and the relationship of these substances to the LAL test remains an important area not described in great detail in compendial or regulatory documents. β-Glucans (beta-glucans) are polysaccharides of D-glucose monomers linked by β-glycosidic bonds. Glucans are important because they can react with certain lysates and cause interference with the LAL test.

In relation to this area of pharmaceutical concern, Tim Sandle has written an introductory paper. It can be accessed here: glucans.

Thursday, 21 February 2013

Cleanrooms are highly controlled environments where the air quality is monitored to ensure the extreme standards of cleanliness required for the manufacture of pharmaceutical, electronic, and healthcare goods. These stringent standards usually require high fresh air rates, extensive filtering, temperature, and humidity control - all of which results in increased energy usage.

Protection from uncontrolled ingress of external ambient air is achieved by creating a pressure differential between the cleanroom and its surroundings. Contamination control is the primary consideration in cleanroom design; however, the relationships between contamination control and airflow are not well understood. Contaminants such as particles or microbes are primarily introduced to cleanrooms by people, although processes in cleanrooms may also introduce contamination. During periods of inactivity or when people are not present, it is possible to reduce airflow and maintain cleanliness conditions.

In relation to the risk assessment of cleanrooms, Tim Sandle has written a free-to-view online paper. Access it here: Sandle cleanrooms.

Wednesday, 20 February 2013

Electron
beam processing, commonly referred to as e-beam, is a sterilisation method which
uses high energy electrons to sterilise an object. In terms of sterilisation technology,
it is a method of irradiation and is sometimes described as electron irradiation
- the act of applying radiation, or radiant energy, to some material.

As
an introduction to the subject, Tim Sandle has written an article for the
journal European Medical Hygiene.

Tuesday, 19 February 2013

Follow this link
to download the extensive 2012 WHO report on tuberculosis. A
comprehensive and up-to-date assessment of the TB epidemic and progress
in implementing and ﬁnancing TB prevention, care and control at global,
regional and country levels using data reported by 204 countries and
territories that account for over 99% of the world’s TB cases.

Monday, 18 February 2013

On 1 April 2013 the National Institute for Biological Standards and Control (NIBSC), currently a centre of the Health Protection Agency (HPA), will join the UK Medicines and Healthcare products Regulatory Agency (MHRA). The two organisations already work closely together and have common interests in managing risks associated with biological medicines, facilitating development of new ones safely and effectively, and maintaining UK expertise in this area.

All other divisions of the Health Protection Agency will transfer to a new body, Public Health England (PHE), on 1 April 2013.

NIBSC and its staff will continue to operate as normal from the present site at South Mimms in Hertfordshire, and NIBSC will continue to use business systems currently hosted by the HPA, though they will now be owned and operated by PHE.

The
primary risk to the immunocompromised patient arises from nosocomial infections
(or hospital acquired infections). A risk to patients additionally can arise
from administered medicines. Until the late 1990s the primary risk was
generally regarded as arising from bacteria. However, since 2001 the second
most common recall for pharmaceutical medicines has been due to fungal
contamination. Moulds are ubiquitous in nature and, therefore they pose a risk
to pharmaceutical manufacturing operations. Aspergillus
spp., Penicillium spp., Trychophyton spp., and other
filamentous fungi have, in some cases, caused significant microbial
contamination issues in production environments and manufactured products.

Saturday, 16 February 2013

The current issue of the GMP Review contains an article titled “Good Practices for Pharmaceutical Microbiology Laboratories”. The article is a critical review of the 2011 WHO document on this important subject. The article has been written by Tim Sandle.

An extract from the article reads:

“The WHO document has a relatively narrow scope in terms of the perceived activities of a pharmaceutical microbiology laboratory and the scope is certainly inwards, in terms of the way a laboratory is run, rather than focusing outwards on the activities which laboratory staff might undertake. For example, the document is concerned with viable microbiological environmental monitoring within the laboratory but not with the activities of microbiology staff going into process areas to take airborne particle counts and to collect viable monitoring samples. This seems a little limited since the case for monitoring in an unclassified laboratory is somewhat debatable and the latter is something which occupies the time of many laboratory staff.”

Friday, 15 February 2013

ISO
15189:2012 ‘Medical laboratories — Particular requirements for quality and
competence’ is a new standard intended to improve the quality and reliability
of medical laboratories. The standard aims to provide advice to clinicians; and
cover such areas as collection, transport, reception, and examination of
samples and finishing with their reporting and interpretation.

Thursday, 14 February 2013

Cleaning
validation is a requirement in industries such as pharmaceutical manufacturing
which adhere to Good Manufacturing Practice (GMP) and Quality Systems
Regulations (QSR), and is specific to the cleaning method and cleaner employed.
Simply stated, validation is a documented guarantee that cleaning can be
performed reliably and repeatedly to satisfy a predetermined level of
cleanliness. Validation is achieved by demonstrating at least three times that
the cleaning process removes residues down to acceptable levels.

Wednesday, 13 February 2013

The
impact of copper surfaces has been found to have a ‘halo’ effect on surrounding
non-copper materials, helping to reduce the presence of bacteria in healthcare
environments, new research has found.

Several
studies have been published during 2012 showed the efficacy of copper and
copper alloys in reducing, or in some cases completely eradicating, bacteria on
key touch surfaces in hospitals.

Further
research carried out in the neonatal intensive care unit (ICU) at Aghia Sofia
Children’s Hospital in Greece shows that, as well as contamination being 90%
lower on copper surfaces, they also exert a ‘halo’ effect, with non-copper
surfaces up to 50cm away also exhibiting a reduction of around 70% compared to
surfaces not in such close proximity.

Tuesday, 12 February 2013

Citizen science involves people participating in both scientific thinking and data collection. One of several citizen science bodies around the world, the UK-EOF, describes the activity as:

“Volunteer collection of biodiversity and environmental data which contributes to expanding our knowledge of the natural environment, including biological monitoring and the collection or interpretation of environmental observations.”

Surprisingly, there are not many citizen science projects in
microbiology even though microbes are of interest to the majority of the
public, as well as being tractable for these kinds of studies.

However, now, in relation to the popularity of this growing trend, the American Society for Microbiology (ASM) is to host a session at a conference in May.

According to the ASM:

"This is going to rock. Citizen microbiology – highlighted at the
American Society for Microbiology Annual Meeting in Denver in May. The
details on the session are below. Sunday May 19 at the American Society
for Microbiology General Meeting in Denver. If you are interested in
attending Register here. If you work on some aspect of Citizen Microbiology please consider submitting an abstract for a talk or poster. The deadline is January 15 17.
We will highlight ALL accepted abstracts in some way both during the
session and in blogs, tweets, interviews, etc. So please consider
participating."

Friday, 8 February 2013

Risk identification in the manufacture of different medicinal products in shared facilities

The European Medicines Agency has published a draft document titled: “EMA: Guideline - setting health based limits for risk identification in the manufacture of different medicinal products in shared facilities”. According to the guide: “When different medicinal products are produced in shared facilities, the potential for cross contamination becomes an issue for concern.” The guide attempts to set out regulatory advice in relation to this. CHMP / CVMP has published this document for comment by 30 June 2013.

A
new device called a soft x-ray electrostatic precipitator protected
immune-compromised mice from airborne pathogenic bacteria, viruses, ultrafine
particles, and allergens, according to a paper published online ahead of print
in the journal Applied and Environmental Microbiology. The SXC ESP device
multiple potential uses, and Washington University is working on licensing the
technology.

"Small
particles are difficult to remove, and our device overcomes that barrier,"
says Pratim Biswas of Washington University, St. Louis. "The device not
only captures particles with a high level of efficiency that has never before
been achieved; it also inactivates them. Even bioterror agents are blocked and
completely inactivated."

The
range of potential uses includes indoor protection of susceptible populations,
such as people with respiratory illness or inhalation-induced allergies, and
young children; protection of buildings from bio-terror attack; protection of
individuals in hospital surgical theaters (for example, during open organ
surgery); protection in cleanrooms for semiconductor fabrication; removal of
ultrafine particles in power plants; and capture of diesel exhaust
particulates.

The
device could be used in homes, with a cost similar to that of high efficiency
air cleaners. It could also be added into stand-alone indoor air cleaners, or
incorporated into HVAC systems in homes, offices, and aircraft cabins. In the
study, the device exceeded standards for high efficiency articulate air
filters, which must be capable of removing particles larger than 0.3
micrometers with 99.97 percent efficiency.

The
SXC ESP works by placing a charge on the particles and then using an electrical
field to trap the particles. The SXC unit then also completely inactivates
biological particles by irradiating them and photoionizing them—as UV light
does, only more energetically.

Monday, 4 February 2013

The
American Society for Microbiology have issued an interesting report titled “Microbes
in Pipes: The Microbiology of the Water Distribution System”.

According
to ASM: “Most microbes in distribution systems probably do not pose health
threats, but when they form biofilms, they can cause physical damage such as
corroding pipes and blocking valves. In addition to forming biofilms, some
non-pathogenic microorganisms can break down chemicals used to minimize
microbial growth and others may release nutrients into the distribution system
that support downstream growth of opportunistic pathogens. The extent to which
these processes occur in water distribution systems is largely unknown, because
these ecosystems have not been characterized.”

Sunday, 3 February 2013

An antibiotic is an agent that either kills or inhibits the growth of a microorganism. This useful infographic outlines some of the major categories of antibiotics available to healthcare practitioners.

The successful outcome of antimicrobial therapy with antibacterial compounds depends on several factors. These include host defense mechanisms, the location of infection, and the pharmacokinetic and pharmacodynamic properties of the antibacterial. A bactericidal activity of antibacterials may depend on the bacterial growth phase, and it often requires ongoing metabolic activity and division of bacterial cells.

Antibacterial antibiotics are commonly classified based on their mechanism of action, chemical structure, or spectrum of activity. Most target bacterial functions or growth processes. Those that target the bacterial cell wall (penicillins and cephalosporins) or the cell membrane (polymyxins), or interfere with essential bacterial enzymes (rifamycins, lipiarmycins, quinolones, and sulfonamides) have bactericidal activities. Those that target protein synthesis (macrolides,lincosamides and tetracyclines) are usually bacteriostatic (with the exception of bactericidal aminoglycosides).

Further categorization is based on their target specificity. "Narrow-spectrum" antibacterial antibiotics target specific types of bacteria, such as Gram-negative or Gram-positive bacteria, whereas broad-spectrum antibiotics affect a wide range of bacteria. Following a 40-year hiatus in discovering new classes of antibacterial compounds, four new classes of antibacterial antibiotics have been brought into clinical use: cyclic lipopeptides (such as daptomycin), glycylcyclines (such as tigecycline), oxazolidinones (such aslinezolid), and lipiarmycins (such as fidaxomicin).

Antibiotic resistance is a form of drug resistance whereby some (or, less commonly, all) sub-populations of a microorganism, usually a bacterial species, are able to survive after exposure to one or more antibiotics; pathogens resistant to multiple antibiotics are considered multidrug resistant(MDR) or, more colloquially, superbugs.

Nowadays fewer new antibiotics are being developed, meaning we have fewer options and stronger and stronger drugs in our antibiotics armory have to be used to treat common infections once they become resistant. This means we are now facing a possible future situation where we will be without effective antibiotics.

Antimicrobial resistance is a responsibility of each and every one of us, be it a patient, healthcare professional or policy maker. This is the theme of an interesting article in the journal European Hospital.

The article states:

“In the past four years, in more than a third of EU/EEA countries, there has been a significant increase in the trend towards combined resistance to both Klebsiella pneumoniae and E. Coli; on a more positive note methicillin- resistant Staphylococcus aureus (MRSA) has shown a decrease or stabilization in most European countries.”

The seven most important measures for dealing with antimicrobial resistance are:

making sure antimicrobials are used appropriately in both humans and animals